Increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area during cocaine abstinence is associated with increased histone acetylation at BDNF exon I-containing promoters.
Increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area during cocaine abstinence is associated with increased histone acetylation at BDNF exon I-containing promoters.
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DOI：
10.1111/j.1471-4159.2011.07571.x
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发表时间：
2012-01
影响因子：
4.7
通讯作者：
Sadri-Vakili G
中科院分区：
文献类型：
--
作者：
Schmidt HD;Sangrey GR;Darnell SB;Schassburger RL;Cha JH;Pierce RC;Sadri-Vakili G
最近的证据表明，在慢性可卡因暴露后长期戒毒期间持续寻找可卡因，部分是通过中脑边缘多巴胺系统的神经适应来调节的。具体地说，可卡因寻找行为的孵化与腹侧被盖区(VTA)脑源性神经营养因子(BDNF)蛋白表达的增加相一致。然而，调控可卡因戒断过程中VTA BDNF蛋白表达随时间变化的分子机制尚不清楚。这些实验的目的是确定可卡因戒断后VTA BDNF转录水平是否发生变化，并确定调控可卡因诱导的VTA BDNF转录变化的分子机制。允许大鼠自行注射可卡因(0.25 mg/次，静脉注射)。按固定比例强化治疗14天，然后强制戒毒7天。与生理盐水对照组相比，强制戒毒7天后，可卡因依赖大鼠VTA中BDNF蛋白和含有外显子I的转录本显著增加。可卡因诱导的BDNF mRNA的改变与组蛋白3(AcH3)的乙酰化和CREB结合蛋白(CBP)与VTA中含有外显子I的启动子结合有关。综上所述，这些结果表明，可卡因自我给药后戒毒重塑了VTA中的染色质，导致BDNF表达增加，这可能有助于对可卡因渴望和复发的神经适应。
Recent evidence suggests that the persistence of cocaine seeking during periods of protracted drug abstinence following chronic cocaine exposure is mediated, in part, by neuroadaptations in the mesolimbic dopamine system. Specifically, incubation of cocaine-seeking behavior coincides with increased brain-derived neurotrophic factor (BDNF) protein expression in the ventral tegmental area (VTA). However, the molecular mechanisms that regulate time-dependent changes in VTA BDNF protein expression during cocaine abstinence are unclear. The goal of these experiments was to determine whether VTA BDNF transcript levels are altered following cocaine abstinence and identify the molecular mechanisms regulating cocaine-induced changes in VTA BDNF transcription. Rats were allowed to self-administer cocaine (0.25 mg/infusion, i.v.) for 14 d on a fixed-ratio schedule of reinforcement followed by 7 days of forced drug abstinence. BDNF protein and exon I-containing transcripts were significantly increased in the VTA of cocaine-experienced rats following 7 days of forced drug abstinence compared to yoked saline controls. Cocaine-induced changes in BDNF mRNA were associated with increased acetylation of histone 3 (AcH3) and binding of CREB binding protein (CBP) to exon I-containing promoters in the VTA. Taken together, these results suggest that drug abstinence following cocaine self-administration remodels chromatin in the VTA resulting in increased expression of BDNF, which may contribute to neuroadaptations underlying cocaine craving and relapse.
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影响因子：
5.8
作者：
Keppler BR;Archer TK
通讯作者：
Archer TK
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
7.6
作者：
Freeman, Willard M.;Patel, Kruti M.;Vrana, Kent E.
通讯作者：
Vrana, Kent E.
影响因子：
3.4
作者：
Le Foll, B;Francès, H;Sokoloff, P
通讯作者：
Sokoloff, P
影响因子：
5.3
作者：
Brami-Cherrier, K;Valjent, E;Caboche, J
通讯作者：
Caboche, J